Comparative Neuromuscular Laboratory

NEUROMUSCULAR CASE OF THE MONTH - OCTOBER 2002

Insulinoma and Peripheral Neuropathy in a
7 year old FS Golden Retriever
Contributed by Dr. Peter Brofman
The Ohio State University
Columbus, OH

Clinical History
An eight-year-old FS Golden retriever presented for evaluation of 4 grand mal seizures over a 6 week period and 10 episodes of disorientation interictally. There was also a 4 week history of progressive tetraparesis, progressing to a non-ambulatory state 2 days prior to admission.

Physical and Neurological Examination
The dog presented in lateral recumbency but was bright, alert, and appropriate. Neurologic examination abnormalities included a grade 2/5 tetraparesis with intact conscious proprioception. Hopping and hemistanding were absent unless she was supported. She was hypotonic with decreased withdrawal reflexes in all four limbs and decreased to absent myotatic reflexes. There was no spinal hyperpathia or sensory deficits. A panniculus reflex could not be elicited. The rest of the physical examination was normal.

Diagnostic Tests
CBC: Normal
Chemistry profile: Hypoglycemia (BG=26, N=77-126)
Urine analysis: Normal
Total thyroxine level: Normal
ACTH stimulation test: Normal
Pre- and post-prandial bile acids: Normal
Acetylcholine receptor antibody titer: Negative
Insulin level (while hypoglycemic: 1700 pmol/L (58-229)
Abdominal ultrasound: Normal
Thoracic radiographs: Normal

Electrodiagnostics
There were spontaneous potentials (positive sharps and fibrillation potentials) in all muscles tested in the right forelimb, left hindlimb, and epaxial muscles. Motor nerve conduction velocities for the left sciatic and right ulnar nerves were 51.7m/s and 55.5m/s, respectively. Compound muscle action potential amplitudes for the same nerves were 9.84mV and 5.41mV, respectively. Repetitive nerve stimulation did not demonstrate a decrement. F-ratio for the sciatic nerve was 2.0.

Muscle and Nerve Biopsies
Moderate generalized myofiber atrophy was present within a cranial tibial muscle biopsy specimen with retention of the normal mosaic pattern of muscle fiber types. Chronic, severe axonal degeneration, subperineurial edema, numerous foamy macrophages, and myelin ovoids were present within the peroneal nerve biopsy (Figs. 1,2; toluidine blue basic fuschin).

Figure 1

Figure 2.

Course and Outcome
An insulinoma with paraneoplastic neuropathy was suspected. A laparotomy was performed and revealed a 5mm mass associated with the distal left limb of the pancreas and associated lymph nodes. It was resected and histopathology was consistent with an islet cell carcinoma with local lymph node metastasis. There was no evidence of hepatic disease grossly or on histopathology. Following surgery, the dog became ketoacidotic, but this resolved with insulin therapy. One month following surgery, the dog was able to ambulate on her own, and was running around normally by 8 weeks. Nine months post-operatively, the dog is still diabetic and receiving insulin with no residual signs of a neuropathy.

Several cases of polyneuropathy associated with insulinoma are in the literature with reports of favorable responses to surgical, corticosteroid, and streptozocin therapies (Chrisman 1980; Shahar et al 1985; Jefferey et al 1994; Van Ham et al 1997; Moore et al 2002). While these therapies may prolong life significantly, there is usually reoccurrence.

UPDATE: The dog was clinically asymptomatic until April 2004 when it represented to The Ohio State University with the first recurrence of hypoglycemia.This was almost 2 years since the initial diagnosis of insulinoma. The dog is being managed medically.

Chrisman CL (1980) Postoperative results and complications of insulinomas in dogs. J Am Anim Hosp Assoc 16:677-684.

Jeffery ND, Mayhew IG, Phillips SM (1994) Letter. Prog Vet Neurol 5:135.

Moore AS, Nelson RW, Henry CJ, Rassnick KM et al (2002) Streptozocin for treatment of pancreatic islet cell tumors in dogs: 17 cases (1989-1999). J Am Vet Med Assoc 221:811-818.

Shahar R, Rousseaux C, Steiss J (1985) Peripheral polyneuropathy in a dog with functional islet B-cell tumor and widespread metastasis. J Am Vet Med Assoc 187:175-177.

Van Ham L, Braund KG, Roels S et al (1997). Treatment of a dog with an insulinoma-related peripheral polyneuropathy with corticosteroids. Vet Rec 141:98-100.